Amifostine (2 brand names, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- AMIFOSTINE
- ETHYOL
Contraindications
ETHYOL is contraindicated in patients with known hypersensitivity to aminothiol compounds.
Adverse Reactions
The following serious adverse reactions are discussed in greater detail in other sections of the labeling: – Hypotension and Cardiovascular Events [see Warnings and Precautions (5.3)] – Severe Cutaneous Reactions [see Warnings and Precautions (5.4)] – Hypersensitivity [see Warnings and Precautions (5.5) ] – Nausea and Vomiting [see Warnings and Precautions (5.6)] – Hypocalcemia [see Warnings and Precautions (5.7)]
Drug Interactions
Closely monitor patients receiving anti-hypertensive medications or other drugs that could cause or potentiate hypotension.
Mechanism of Action
ETHYOL is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite. This metabolite is believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. The ability of ETHYOL to differentially protect normal tissues is attributed to the higher capillary alkaline phosphatase activity, higher pH and better vascularity of normal tissues relative to tumor tissue, which results in a more rapid generation of the active thiol metabolite as well as a higher rate constant for uptake into cells. The higher concentration of the thiol metabolite in normal tissues is available to bind to, and thereby detoxify, reactive metabolites of cisplatin. This thiol metabolite can also scavenge reactive oxygen species generated by exposure to either cisplatin or radiation.
Overdosage
In clinical trials, the maximum single dose of ETHYOL was 1300 mg/m 2. No information is available on single doses higher than this in adults. At the higher doses, anxiety and reversible urinary retention occurred. The most likely symptom of overdosage is hypotension, which should be managed by infusion of normal saline and other supportive measures, as clinically indicated [see Warnings and Precautions (5.3)] .